Enhanced Inflammasome Activity in Patients with Psoriasis Promotes Systemic Inflammation

Psoriasis is linked to systemic inflammation and cardiovascular comorbidities, but studies of the underlying cellular mechanisms are lacking. The NLRP3 inflammasome genetically associated with psoriasis, its activation increasingly disease. In this study, we show that patients psoriasis exhibited higher plasma levels inflammasome-generated IL-1? IL-18, without any correlation skin lesion severity. Increased constitutive expression sensors NLRP3, NLRP1, AIM2 was found in peripheral blood cells also those mild disease, accompanied by an increased caspase-1 reactivity myeloid subsets. TNF-? activate selectively requirement for a priming signal. signal through TNFR?caspase-8?caspase-1 alternative pathway, which proceeds independently pyroptosis. Patients who received anti-TNF therapy had normalized IL-18 as well reactivity. This contrast treated methotrexate persistent, Thus, TNF-?–mediated inflammasomes may contribute inflammation. Anti-TNF function, suggesting mechanism risk?reducing effect.